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There are many conditions that come under the 'dysmelia' heading or involve dysmelia as one of its features. Listed below are many of them. If you know of one that isn't covered, or have information to add, please let us know. The links are to reputable sources, mainly Orphanet, where you can find out more about the specific condition.
Humeroradial synostosis may occur sporadically or as an extremely rare inheritable disorder. The current classification divides cases into class I (fixed in extension with ulnar ray hypoplasia) or class II (fixed in flexion without hypoplasia).
Link: Humeroradial Synostosis
Radial club hand or radial dysplasia describes a very rare congential failure of formation of preaxial structures in the upper limb. At its extreme; the most obvious abnormality is that of the skeleton with a hypoplastic or absent radius. However; all soft tissues may be affected.
Link: Radial Aplasia
8q13 microdeletion syndrome
Mesomelia-synostoses syndrome (MSS) or mesomelic dysplasia with acral synostoses Verloes-David-Pfeiffer type is a rare autosomal-dominant disorder characterized by mesomelic limb shortening; acral synostoses; and multiple congenital malformations. So far; five patients in four unrelated families have been reported worldwide with MMS. By using whole-genome oligonucleotide array CGH; we have identified an interstitial deletion at 8q13 in all patients.
Adams-Oliver Syndrome (AOS) is a rare disorder characterized by the combination of congenital limb abnormalities and scalp defects, often accompanied by skull ossification defects. The prevalence is unknown. The severity of the disorder varies greatly among affected individuals. Aplasia cutis congenita, transverse limb defects and cutis marmorata telangiectica are characteristic of this condition. The affected patients typically have malformations of the hands, arms, feet and/or legs that range from hypoplastic fingers and toes to absent hands and/or lower legs, and occasionally show intellectual deficit. AOS may be associated with a variety of physical anomalies including congenital cataract, strabismus and microphthalmia, congenital heart malformations (including tetralogy of Fallot and pulmonary atresia), and hepatoportal sclerosis. Hydrocephalus is the principal cerebral feature and epilepsy may be associated. Extensive lethal anomalies are possible. The etiopathogenesis remains unclear. Most cases are transmitted as an autosomal dominant trait, but some show autosomal recessive transmission with familial or sporadic occurrence. Limb and scalp defects require orthopedic treatment. Management requires a comprehensive multidisciplinary approach. (Source: Orphanet)
Link: Adams-Oliver syndrome
Aglossia adactylia is characterized by the association of aglossia (absence of tongue), adactylia (absence of fingers or toes) and limb, craniofacial and other, less frequent malformations. It was first described in 1932, but in 1950 Hanhart described three cases of aglossia with associated limb defects and gave his name to the syndrome. Several similar cases have since been reported allowing a better definition of the associated malformations. Craniofacial anomalies include microstomia (small mouth), micrognathia, hypoglossia, variable clefting or aberrant attachments of tongue, mandibular hypodontia, cleft palate, cranial nerve palsies (including Möebius sequence), broad nose, telecanthus, lower eyelid defects, and facial asymmetry. The limb defects are represented by hypoplasia, varying from absence of the distal phalanx to total adactyly or partial limb amputation, with or without syndactyly. Limb defects usually involve all four limbs. Among the less constant malformations are gastroschisis and splenogonadal fusion. Intelligence and stature are generally normal, but patients with intellectual deficit have been reported. Early feeding and speech difficulties may occur. Some of the listed symptoms may be confounded with those of Nager syndrome or acro-facial dysostosis. Both Nager syndrome and acro-facial dysostosis differ from aglossia adactylia in the kind of facial dysmorphia (in Nager syndrome the ears are malformed and malar hypoplasia is associated with downslanting palpebral fissures) and in the type of limb anomalies (preaxial defects are more common in Nager syndrome whereas transverse defects are more common in aglossia-adactyly). About 30 cases of Hanhart syndrome were reported in the literature between 1932 and 1991, and a few cases of intra-familial recurrence led to a hypothesis of mutation of an autosomal recessive gene being responsible for this condition. This genetic hypothesis, disproved in 1973, has now been replaced by a more plausible hypothesis: the abnormalities are probably the disruptive consequence of hemorrhagic lesions occurring during development. Vascular problems presumed to result from these lesions would be more likely to occur in distal regions, such as the distal limbs, tongue, and occasionally parts of the brain. Chorionic villous sampling (CVS), when performed before week 10 of amenorrhoea, has been associated with this disorder, giving further credence to a disruptive vascular hypothesis. The features described in patients diagnosed with aglossia adactylia after CVS are generally of lower severity than those described in patients with the Hanhart syndrome, but these two conditions probably belong to the same spectrum of anomalies. Since the association between early CVS and oromandibular limb dysgenesis has been confirmed, CVS is now performed later in pregnancy, and cases of this disruptive malformation are currently rarely reported in the literature. Treatment may involve orthopedic and/or plastic surgery for the limb anomalies. (Source: Orphanet)
Link: Aglossia adactylia
Autosomal recessive amelia is characterised by the absence of the upper limbs and severe underdevelopment of the lower limbs. Minor facial abnormalities (depressed nasal root; upturned nose; infra-orbital creases; prominent cheeks and micrognathia) were also reported.
Amniotic band syndrome
Amniotic bands are included in the amnion rupture sequence that comprises a series of malformations, the denomination of which depends on the etiologic hypothesis. The observed anomalies are thought to be due to a rupture of the amnion during the first trimester of gestation, resulting in adhesions between the amnion and the fetal skin, and in some cases, small strands of amnion encircling developing limbs, leading to annular constrictions, and bands between torn amnion and chorionic mesenchyme. Besides annular constrictions, pseudo-syndactyly, intra-uterine amputations, and umbilical cord constrictions may also be seen. In addition, the decrease in amniotic fluid and/or a possible tethering of a limb by an amniotic band may result in a decrease in fetal movements, and in scoliosis, foot deformity, lung hypoplasia, and hydrops. The amnion rupture sequence is rare, occurring in 1 to 4 newborns in 100,000. It is a sporadic disease, with rare exceptions: a few affected families have been described, with a likely autosomal dominant heredity. The clinical features of affected individuals from these rare families do not differ from those of the sporadic cases: no two affected foetuses will have exactly the same features, and there is no single feature that consistently occurs. Examination of the placenta and membranes leads to the diagnosis, which is made when aberrant bands are observed and possible remnants are noted at the placental base of the umbilical cord. The amnion rupture sequence must be differentiated from the Adams Oliver syndrome, an autosomal dominant anomaly characterized by transverse limb reduction defects, aplasia cutis congenita over the posterior parietal region with an underlying bone defect, and cutis marmorata. Although the pathogenesis of the amnion rupture sequence is still being debated, it is accepted by most authors that it has a pathogenetic mechanism different from that of the limb body wall complex (LBWC). The LBWC associates severe limb reduction defects, thoracic and/or abdominal coelosomia and unusual facial clefts with amnion adhesions, encephalocele or exencephaly. (Source: Orphanet)
Link: Amniotic band syndrome
Apert syndrome is a malformation disorder characterised by the association of faciocraniosynostosis and osseous and membranous syndactyly of the four extremities. The incidence has been estimated at 1 in 50 000 births. The craniosynostosis is bicoronal and is evident at birth. The longitudinal system (sagittal and metopic sutures) is abnormally broad, even in the first few months of life. The superior maxilla is severely hypoplastic, resulting in malocclusion and a protruding lower jaw. The face is usually broad with a beaked nose. Ocular abnormalities include hypertelorism and sometimes severe exophthalmos. Syndactyly of the fingers and toes may be total (mitten hands and sock feet) or partial affecting the second, third, and fourth digits. Intellectual deficit is frequent and often severe, usually being associated with cerebral malformations. Nearly 50% of patients have increased intracranial pressure. The majority of patients (more than 98%) carry a mutation (Ser252Trp or Pro253Arg) in the gene encoding fibroblast growth factor receptor type 2 (FGFR2). Alu-element insertion mutations in or near exon 9 of FGFR2 are responsible for the remaining cases. Early intervention for craniosynostosis (before the age of six months) may improve the mental prognosis: a significant number of patients who underwent early surgical intervention later showed normal intellectual performance. Correction of the maxillary hypoplasia and hypertelorism should not be carried out until the patient is at least four years old (except in severe cases). (Source: Orphanet)
Link: Apert Syndrome
Autosomal recessive amelia
Autosomal recessive amelia is characterised by the absence of the upper limbs and severe underdevelopment of the lower limbs. Minor facial abnormalities (depressed nasal root; upturned nose; infra-orbital creases; prominent cheeks and micrognathia) were also reported. The syndrome has been described in three foetuses born to non consanguineous parents. (Source: Orphanet)
Autosomal recessive Robinow syndrome
(Costovertebral segmentation defect - mesomelia)
Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS; see this term) characterized by short-limb dwarfism; costovertebral segmentation defects and abnormalities of the head; face and external genitalia. Fewer than 100 cases of this type have been reported in the literature to date. The disorder is usually recognizable at birth or in early childhood. The clinical signs are generally far more severe in recessive cases of RS than in the dominant form; particularly skeletal abnormalities. All patients with the recessive form of RS suffer from vertebral segmentation abnormalities; resulting in scoliosis and chest deformities. Rib fusions are considered to be characteristic of the autosomal recessive form. The syndrome is caused by mutations in the.ROR2.gene (9q22). Transmission is autosomal recessive. (Source: Orphanet)
Brachydactyly ('short digits') is a general term that refers to disproportionately short fingers and toes; and forms part of the group of limb malformations characterized by bone dysostosis. The various types of isolated brachydactyly are rare; except for types A3 and D. Brachydactyly can occur either as an isolated malformation or as part of a complex malformation syndrome. To date; many different forms of brachydactyly have been identified.
Campomelia; Cumming type
Campomelia; Cumming type; is characterized by the association of limb defects and multivisceral anomalies. The syndrome has been reported in eight infants from four different families. Skeletal features include tetramelic campomelia and short long bones. Extraskeletal manifestations may include cervical lymphocele; generalized hydrops; polycystic kidneys; pancreas and liver; fibrotic liver or pancreas; polysplenia; heterotaxia; lung hypoplastia; short bowel. All infants reported so far were either stillborn or died shortly after birth. In one of the affected families; three sibs with identical features born to first-cousin parents have been reported; suggestive of autosomal recessive mode of inheritance. (Source: Orphanet)
Link: Campomelia; Cumming type
Cenani-Lenz syndrome (CLS) is a congenital malformation syndrome that associates a complex syndactyly of the hands with malformations of the forearm bones and similar manifestations in the lower limbs.
Fewer than 30 cases have been described and the exact incidence has not been evaluated. The majority of cases occurred in related families.
Classical CLS is characterized by the almost symmetrical presence of a total fusion of fingers and synostosis of the hand bones, giving the hands a mitten-like appearance. A variant of the syndrome, with oligodactyly and partial syndactyly, has been reported. The following features characterize the syndrome: carpal, metacarpal and digital synostoses, disorganization of the carpal bones, numeric reduction of the digital rays and toe syndactyly. Other features are radioulnar synostosis with shortening of the radius and ulna, brachymesomelia, radius head dislocation and metatarsal synostoses. The syndrome affects both the upper and lower limbs but, in general, the latter are less severely affected. Associated malformations (renal hypoplasia and vertebral and hemivertebral anomalies) have occasionally been reported. A few publications associate CLS with other, more frequent, forms of syndactyly. Mild facial dysmorphism (ptosis, high-arched palate, high, broad and prominent forehead, hypertelorism, flat nasal bridge, down slanting palpebral fissures, short nose, short prominent philtrum and malar hypoplasia) has been described in isolated cases.
The disease is transmitted as an autosomal recessive trait. Homozygous or compound heterozygous mutations of the LRP4 gene (11p12-p11.2) have been identified. A heterozygous duplication of 1.7 Mb covering the GREM1 and FMN1 genes has also been reported in a CLS-like form of the syndrome.
Diagnosis is essentially clinical.
CLS can be distinguished clinically from other limb malformations.
Diagnosis can be suspected antenatally by ultrasonography. As an autosomal recessive syndrome, recurrence risk for CLS is 25% for a subsequent pregnancy.
Surgical treatment with reconstruction of an individualized finger is recommended but the functional results of syndactyly release may be unsatisfactory.
Functional prognosis depends on the specific limb anomalies of the patient. (Source: Orphanet
Link: Cenani-Lenz syndrome
Ectrodactyly - split hand-foot malformation, SHFM
Split hand-split foot (split hand-foot malformation, SHFM) is a rare malformation involving the central rays of the hands and feet, affecting randomly one to all four limbs. Syndactyly with oligodactyly, median clefts of the hands and feet, and opposable fingers are the most common features, leading to a so-called 'lobster claw' appearance. The major feature observed is monodactyly, where the radial rays are absent with, as a rule, only the fifth digit remaining. Non-syndromic forms are usually isolated but there have been rare reports of an association with deafness. The malformation has also been observed with aniridia and Alport syndrome. Management includes surgical reduction of the malformation and orthesis. Five loci for SHFM have been mapped: SHFM1 on chromosome 7, SHFM2 on chromosome X, SHFM3 on chromosome 10, SHFM4, which is caused by mutation in the TP63 gene on chromosome 3, and SHFM5 on chromosome 2. Inheritance depends on the genetic localization: SHFM, 3 and 4 have dominant autosomal transmission (with incomplete penetrance), SHFM2 is X-linked recessively inherited. The mode of SHFM 5 transmission is unknown: recessive or dominant inheritance with incomplete penetrance have both been discussed. (Source: Orphanet)
Fibular dimelia - diplopodia
Fibular dimelia accompanied by complete tibial agenesis and mirror polydactyly or foot duplication is a rare developmental anomaly reported in at least 11 cases. It can be isolated or associated with ulnar dimelia; facial abnormalities and sacrococcygeal teratoma. The etiology is unknown; but has been suggested that a teratogenic event occurs as developmental specification reaches the level of the future knee. A central role for the mesenchymal precursor; from which chondro-osseous morphology emerges; has also been suggested. Treatment is surgical and prosthesis is needed in order to improve the quality of life of affected children. (Source: Orphanet)
Fibular hemimelia is a congenital longitudinal limb deficiency characterized by complete or partial absence of the fibula bone.
Prevalence is estimated at 1 in 50,000. A slight male preponderance has been reported in some studies, whereas other reports describe an equal sex distribution.
Unilateral involvement occurs in two-thirds of cases, with the right fibula being affected more often than the left. Agenesis of both fibulae is rare. Fibular hemimelia may vary from partial absence of the fibula (10% of cases) with relatively normal-appearing limbs, to absence of the fibula with marked shortening of the femur, curved tibia, bowing of the leg, knee joint and ankle instability and significant soft tissue deficiency. The major functional deficiency results from leg length discrepancy in unilateral cases or asymmetrical dwarfism in bilateral cases. The foot is generally in an equinovalgus position. As there is limited growing potential within the affected bone, the extent of the deformity tends to increase with growth. Occasionally, fibular hemimelia is associated with congenital shortening of the femur (femur-fibula-ulna complex; see this term). Other skeletal anomalies (craniosynostosis, syndactyly, brachydactyly, oligodactyly and ectrodactyly) may also be present. Fibular hemimelia is also found in several generalized skeletal dysplasias and dysostoses. Rarely, fibular hemimelia is associated with nonskeletal malformations (eye abnormalities such as anterior chamber anomalies or anophthalmia, cardiac anomalies, renal dysplasia, thrombocytopenia, thoracoabdominal schisis, spina bifida and, rarely, intellectual deficit). Fibular hemimelia can be present in some chromosome anomalies.
The etiology is unclear. The deformity is probably due to disruptions during the critical period of embryonic limb development, between 4th and 7th week of gestation. Vascular dysgenesis, viral infections, trauma and environmental influences have been suggested as possible causes.
Diagnosis is based on clinical examination and X-rays.
Differential diagnoses include amniotic band syndrome, thalidomide embryopathy and several skeletal dysplasias and dysostoses with asymmetrical involvement of the lower limbs such as femoral-facial syndrome (see these terms).
Prenatal diagnosis of fibular hemimelia has been reported.
Most cases are sporadic. A family history has been reported in a small percentage of cases with an autosomal dominant pattern of inheritance and incomplete penetrance.
Management requires a multidisciplinary approach (genetic counselors, perinatologists and pediatric orthopedic surgeons). Orthopedic treatment aims at correcting the leg length discrepancy, and, in bilateral cases, correcting the asymmetrical dwarfism. In less severe cases with minimal hypoplasia of the fibula and only mild limb length discrepancy, special shoes and/or accommodative insoles may be used to equalize limb length. In some mild cases, epiphysiodesis on the contralateral (normal) side is also an option. In moderate limb length inequality, limb lengthening is an option but it carries the risk of requiring multiple reconstructive procedures and complications. Rarely, for cases of severe limb length discrepancy or complete absence of the fibula when the foot is nonfunctional, amputation with prosthetic fitting in early childhood may be considered.
Fibular deficiency is usually a benign condition, although in severe cases it can be debilitating. Acceptable functional results may be achieved by surgery. In case of syndromic presentation, prognosis depends on the nature of the associated anomalies. (Source: Orphanet)
Link: Fibular hemimelia
Syndactyly type 4 (SD4) is a very rare congenital distal limb malformation characterized by complete bilateral syndactyly (involving all digits 1 to 5). So far; only four reports have been described in the literature. A frequent association with polydactyly (with six metacarpals and six digits) has been reported. Feet are affected occasionally. The SD4 locus maps to 7q36. The condition is inherited as an autosomal dominant trait. (Source: Orphanet)
Link: Haas syndrome
Aglossia adactylia (Hanhart syndrome) is characterized by the association of aglossia (absence of tongue), adactylia (absence of fingers or toes) and limb, craniofacial and other, less frequent malformations. It was first described in 1932, but in 1950 Hanhart described three cases of aglossia with associated limb defects and gave his name to the syndrome. Several similar cases have since been reported allowing a better definition of the associated malformations. Craniofacial anomalies include microstomia (small mouth), micrognathia, hypoglossia, variable clefting or aberrant attachments of tongue, mandibular hypodontia, cleft palate, cranial nerve palsies (including Möebius sequence), broad nose, telecanthus, lower eyelid defects, and facial asymmetry. The limb defects are represented by hypoplasia, varying from absence of the distal phalanx to total adactyly or partial limb amputation, with or without syndactyly. Limb defects usually involve all four limbs. Among the less constant malformations are gastroschisis and splenogonadal fusion. Intelligence and stature are generally normal, but patients with intellectual deficit have been reported. Early feeding and speech difficulties may occur. Some of the listed symptoms may be confounded with those of Nager syndrome or acro-facial dysostosis. Both Nager syndrome and acro-facial dysostosis differ from aglossia adactylia in the kind of facial dysmorphia (in Nager syndrome the ears are malformed and malar hypoplasia is associated with downslanting palpebral fissures) and in the type of limb anomalies (preaxial defects are more common in Nager syndrome whereas transverse defects are more common in aglossia-adactyly). About 30 cases of Hanhart syndrome were reported in the literature between 1932 and 1991, and a few cases of intra-familial recurrence led to a hypothesis of mutation of an autosomal recessive gene being responsible for this condition. This genetic hypothesis, disproved in 1973, has now been replaced by a more plausible hypothesis: the abnormalities are probably the disruptive consequence of hemorrhagic lesions occurring during development. Vascular problems presumed to result from these lesions would be more likely to occur in distal regions, such as the distal limbs, tongue, and occasionally parts of the brain. Chorionic villous sampling (CVS), when performed before week 10 of amenorrhoea, has been associated with this disorder, giving further credence to a disruptive vascular hypothesis. The features described in patients diagnosed with aglossia adactylia after CVS are generally of lower severity than those described in patients with the Hanhart syndrome, but these two conditions probably belong to the same spectrum of anomalies. Since the association between early CVS and oromandibular limb dysgenesis has been confirmed, CVS is now performed later in pregnancy, and cases of this disruptive malformation are currently rarely reported in the literature. Treatment may involve orthopedic and/or plastic surgery for the limb anomalies. (Source: Orphanet)
Link: Hanhart syndrome
Congenital absence of all or part of the distal half of a limb.
Holt-Oram syndrome (HOS) is characterized by mild-to-severe congenital cardiac defects and skeletal abnormalities of the upper limbs. The most common cardiac disorder is an ostium secundum atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. Electrocardiographical abnormalities such as various degrees of atrioventricular block have also been reported. In addition hypoplastic peripheral vessels of the upper limbs have been observed. Frequent orthopedic signs are radial ray abnormalities, absent or abnormal radius, upper limb-transverse elements missing and various thumb anomalies. One out of 100,000 live births is affected. More than 300 cases have been published, revealing a wide spectrum of clinical signs. HOS is an autosomal dominant disorder with complete penetrance. The underlying genetic defect was found on the long arm of chromosome 12 (12q2). Mutations in the TBX3 and TBX5 genes lead to a wide range of phenotypes. Echocardiography can be used to detect cardiac anomalies in the offspring of a parent with HOS. Genetic counseling is recommended. Surgical operation can be performed in order to treat ASD. (Source: Orphanet)
Link: Holt-Oram syndrome
This syndrome is characterised by the association of Microgastria with a limb reduction defect. Most of the 50 cases of congenital microgastria reported in the literature are associated with other multiple congenital anomalies: limb-reduction defects (unilateral or bilateral absence of the thumbs, absence of the radius and ulna, total amelia), asplenia, intestinal malrotation, hepatic symmetry, cardiopulmonary anomalies, central nervous system and renal anomalies, and laryngo-tracheo-bronchial clefts. Isolated congenital microgastria is an extremely rare condition; only three cases have been reported in the literature so far. The small reservoir capacity of the stomach leads to megaesophagus, an incompetent gastroesophageal sphincter, reluctance to feed, persistent vomiting, malnutrition, and recurrent respiratory tract infections. The outcome for most of the reported patients with severe microgastria was either death or extreme malnutrition. The microgastria-limb reduction association is believed to arise as a result of aberant mesodermal development in the fourth or fifth week of embryonic life but the aetiology of this syndrome is unknown. Arrest of development after about the eighth week of fetal life was supposed in a case of isolated congenital microgastria. A critical role for the notochord was presumed. Three out of 13 cases of microgastria-limb reduction complex involved twins, suggesting that the origin of the disorder may be related to the process of twinning itself. There is no evidence of Mendelian inheritance of microgastria-limb reduction defect. The clinical manifestations of congenital microgastria depend on the stage at which the embryologic development of the stomach is arrested. They are often apparent at birth. In children with severe reflux symptoms since birth, detailed upper gastrointestinal contrast studies should be carried out to check for reduced gastric reservoir capacity. Prolonged medical management is not beneficial in congenital microgastria, because the stomach size does not increase significantly with the passage of time. In the absence of other associated life-threatening congenital anomalies, this condition can be managed successfully with early gastric augmentation leading to toleration of increasing amounts of oral feeding. Early operative treatment (Hunt-Lawrence pouch) improves nutritional management and facilitates the achievement of normal growth and development. (Source: Orphanet)
Microlissencephaly - micromelia
Microlissencephaly-micromelia is characterised by micromelia of the upper limbs; dysmorphic features; seizures; postnatal microcephaly with a simplified gyral pattern and apparent frontal agyria; leading to early death. It has recently been reported in two sisters. Neonatal examination is abnormal with absent archaic reflex. Patients develop intractable seizures. Hypoparathyroidism and hypertrichosis can also be present. Inheritance is consistent with an autosomal recessive pattern. Medical management requires neonatal intensive care. (Source: Orphanet)
A congenital anomaly characterized by the absence of at least one finger or toe.
Phocomelia; Schinzel type
Schinzel phocomelia syndrome; also called limb/pelvis hypoplasia/aplasia syndrome; is characterized by skeletal malformations affecting the ulnae; pelvic bones; fibulae and femora. As the phenotype is similar to that described in the malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome; they are thought to be the same disorder. Only a few cases have been described. Patients have intercalary limb deficiencies (phocomelia sometimes combined with polydactyly; oligodactyly or ectrodactyly); absent or hypoplastic pelvic bones (including sacral agenesis or hypoplasia); skull defects (frequently a defect of the occipital bone with or without meningocele). Additional features may include thoracic dystrophy; unusual facies (dysplastic and large ears; and a high and narrow palate); and genital malformations (Mullerian aplasia; agenesis of the uterus and vagina; micropenis with cryptorchidism). Growth and mental development are normal. As most of the affected patients were born to consanguineous parents; autosomal recessive inheritance is presumed. A null mutation in the 'WNT7A' gene (3p25) is responsible for this syndrome. It is a severe allelic form of Fuhrmann syndrome. The limb deficiencies and/or the absent pelvis may be detected by ultrasound. Some of the affected infants died shortly after birth. (Source: Orphanet)
Poland syndrome is marked by a unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal portion), and a variable degree of ipsilateral hand anomalies, including symbrachydactyly. Various anomalies of the breasts and nipples, and variable involvement of the hand and forearm (some patients having normal hands) have also been reported. The absence of other muscles around the shoulder girdle is a frequent feature . The prevalence at birth is about 1 to 3 per 100 000. Males are more often affected than females. Poland syndrome is most commonly a sporadic condition, but rare familial cases have been reported, compatible with an autosomal dominant mode of inheritance. The syndrome is thought to be of vascular origin, for example a result of a disruption in the blood supply in the subclavian artery. (Source: Orphanet)
Link: Poland syndrome
A congenital anomaly characterized by the presence of more than the normal number of fingers or toes.
A developmental abnormaly in which supernumerary limbs or parts of limbs are present.
A congenital condition in which multiple fingers or toes are webbed.
Radial hemimelia is a congenital longitudinal deficiency of the radius bone of the forearm characterized by partial or total absence of the radius. It occurs in 1/30,000-100,000 live births, and is slightly more common in males than in females (sex ratio of 3:2). Radial hemimelia is bilateral in 50% of cases and the right side is more commonly involved than the left (with a ratio of 2:1). The degree of malformation varies. In the most severe cases, the radius is completely absent, and the entire arm is shorter with marked curving of the forearm and stiffness of the elbow and fingers. This is the most common variant of radial hemimelia, in which hand, finger and elbow function is significantly impaired. In the majority of cases with complete absence of radius, the soft tissues of the forearm (including the muscles, nerves, tendons, ligaments and blood vessels) are also abnormal. There may also be underdevelopment or absence of the thumb, and fusion or malformation of the elbow joint with restricted motion. In the mildest cases, the radius is slightly smaller than the ulna, with minimal deviation at the wrist. Radial hemimelia is frequently associated with other congenital anomalies or syndromes, including chromosomal anomalies (trisomy 13, 18 and 21), Holt-Oram syndrome, Roberts syndrome, Rothmund-Thomson syndrome, thrombocytopenia-absent radius (TAR) syndrome (in which characteristically the thumb is present), Townes-Brocks syndrome, VACTERL association and Fanconi anemia (see these terms). Approximately 5-10% of radial hemimelia cases are familial but the etiology remains unknown. The deformities are believed to develop early in pregnancy, between the 28th and 56th day of gestation. Maternal drug use (cocaine, thalidomide or valproate), compression of the uterus and vascular injury have been suggested to play a role in the etiopathogenesis of this condition, but these theories have not been proven. Diagnosis is based on clinical examination and X-rays. Further tests and a complete physical examination are required in case of additional anomalies. Radial hemimelia can be detected by prenatal ultrasound scan at 20 weeks of gestation. Management aims at reducing the functional deficit. Initial therapy consists of straightening of the hand and stabilization of the wrist by serial splinting or casting that should be undertaken shortly after birth. Intensive stretching exercises and physical therapy are required to achieve a passive extension of the wrist and elbow into a normal position. More severe cases require corrective surgery, usually performed at around one year of age. Surgical approaches involve realigning the ulna bone through osteotomy and use of external fixators, and centering the wrist on the remaining ulna. In case of thumb absence, corrective shifting the index finger to the position of the missing thumb (pollicisation) is used to make the hand functional. (Source: Orphanet)
Link: Radial hemimelia
Roberts syndrome (SC phocomelia)
Roberts syndrome (RBS) is characterized by pre- and postnatal growth retardation, severe symmetric limb reduction defects, craniofacial anomalies and severe intellectual deficit. SC phocomelia is a milder form of RBS. The prevalence and incidence are not known. Less than 150 cases have been described in the literature. Upper limbs are more frequently and severely affected than lower limbs. The defect is mostly mesomelic with the radius being the most affected in the upper limbs, and the fibula in the lower limbs. The most severe defects result in phocomelia. Aplastic or hypoplastic thumbs, oligodactyly, clinodactyly or syndactyly can also occur. Craniofacial anomalies include microcephaly (more severe in males than in females), hypoplastic nasal alae, malar hypoplasia, hypertelorism, micrognathia, capillary hemangioma, exophthalmos, downslanting palpebral fissures, dysplastic or small ears, cloudy cornea or cataracts, and cleft lip and palate. There is a correlation between the degree of limb and facial malformations. Other malformations such as congenital heart defects, cystic kidney and large genitalia (enlarged phallus or clitoris), may occur. Severe intellectual deficit is observed in patients surviving the newborn period. The mode of transmission is autosomal recessive. The disease is caused by mutations in the ESCO2 gene (8p21.1), which encodes a protein belonging to the Eco1/Ctf7 family of acetyltransferases, involved in the establishment of sister chromatid cohesion during S phase. ESCO2 mutations lead to delayed cell division, increased cell death and impaired cell proliferation. The loss of progenitor cells during embryogenesis is likely responsible for the developmental defects observed in RBS. The diagnosis is based on clinical features and karyotyping (with a characteristic ``railroad track'' appearance of chromosomes due to repulsion of heterochromatic regions and premature centromere separation). Direct sequencing of the ESCO2 gene can confirm the diagnosis. Differential diagnoses include thalidomide embryopathy, and the Baller-Gerold, Cornelia de Lange and TAR syndromes (see these terms). When a previous child in the family is diagnosed with RBS and carries ESCO2 mutations, prenatal diagnosis can be performed through DNA analysis of chorionic villus samples. Otherwise, RBS may be suspected by observation of characteristic RBS anomalies at ultrasonography and can be confirmed by karyotyping. Management includes surgical correction of facial malformations, surgical and/or orthopedic treatment of limb defects and management of the cognitive disabilities. Prognosis is relatively unfavorable. High mortality in the newborn period or early childhood is due to cardiac or renal malformations.
Sirenomelia is a rare lethal malformation characterized by severe anomalies of the caudal part of the fetus. The prevalence has been estimated at about 1 in 100;000 births. Malformations include a single lower limb; with various degrees of involvement ranging from single to separate femurs in the same skin shaft; presence of two feet (sympode mermaid) or one foot (monopode mermaid); to absence of both feet (ectromelic mermaid). Urogenital anomalies are also present and include bilateral renal agenesis; absence of outflow tract and absence of external genitalia. Imperforate anus and sacro-coccygeal agenesis have also been reported. Together these malformations comprise the extreme form of the caudal regression sequence. Sirenomelia is usually a sporadic condition but rare familial recurrences have been described. (Source: Orphanet)
Symbrachydactyly is a congenital (present at birth) hand anomaly; which affects a single upper limb. It is not inherited. It is characterised by short, stiff, webbed or missing fingers. The underlying muscles, tendons, ligaments and bones are all affected.
Syndactyly is condition wherein there is a congenital malformation of the limbs that is characterised by the webbing of two fingers. It occurs in 1 in 2000 to 3000 live births. The term is derived from the Greek words .syn.; which means together; and .dactyly.; which stands for fingers.
Tetraamelia - multiple malformations
Tetra-amelia syndrome is a very rare disorder characterized by the absence of all four limbs. This syndrome can also cause severe malformations of other parts of the body; including the face and head; heart; nervous system; skeleton; and genitalia. The lungs are underdeveloped in many cases; which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems; most are stillborn or die shortly after birth
Tibial aplasia - ectrodactyly
(Tibial hemimelia-ectrodactyly syndrome)
Tibial aplasia-ectrodactyly syndrome is a rare condition characterized by congenital ectrodactylous limb malformations associated with tibial aplasia or hypoplasia. The incidence is estimated to be approximately 1 in 1;000;000 live births. The expression of the phenotype is highly variable and ranges from bilateral aplasia of tibiae and split-hand/split-foot deformity (tetramonodactyly or transverse hemimelia) to the mildest visible manifestation; hypoplastic big toes. Additional malformations may include distal hypoplasia or bifurcation of femora; hypo- or aplasia of ulnae; and minor anomalies such as aplasia of patellae; postaxial and intermediate polydactyly in association with split-hand deformity; and cup-shaped ears. Overlap with the Gollop-Wolfgang syndrome (see this term) has been described. The syndrome is generally inherited in an autosomal dominant manner with reduced penetrance. Autosomal recessive inheritance has also been proposed in some families. Two susceptibility loci at 1q42.2-q43 and 6q14.1 have been identified; leading to the hypothesis that this syndrome fits the model of digenic inheritance.
Tibial hemimelia is a rare congenital anomaly characterized by deficiency of the tibia with a relatively intact fibula. Prevalence is estimated at 1 in 1;000;000 live births. Tibial hemimelia can be unilateral or bilateral. It may occur as an isolated anomaly; or as a part of a complex malformation syndrome (such as the Gollop-Wolfgang complex and triphalangeal thumb-polysyndactyly syndrome; see these terms). The etiology remains uncertain. Although the majority of cases with tibial hemimelia are sporadic; affected families with possible autosomal dominant or autosomal recessive inheritance have been reported. Diagnosis is based on clinical and radiological findings. Prenatal diagnosis using ultrasound is possible. Management requires surgical correction of the tibial hemimelia and any associated malformations; especially those concerning the foot (equinovarus; partial duplication of the foot). Reconstructive surgery and a prosthesis adapted to growth; together with regular post-operative follow-up; are necessary for optimal functional results. (Source: Orphanet)
Link: Tibial hemimelia
Trisomy 18 syndrome
Trisomy 18 is a chromosomal abnormality associated with the presence of an extra chromosome 18 and characterized by growth delay, dolichocephaly, a characteristic facies, limb anomalies and visceral malformations. Incidence is estimated at between 1/6000 and 1/8000 births. In utero death occurs in more than 95% of fetuses with this chromosome anomaly. For unknown reasons, the rate of survival is higher in females than in males, leading to a female predominance among live-born trisomy 18 infants. Hypotonia, hyporeactivity and feeding problems (poor suction) are present in the first weeks of life and are followed by a progression to hypertonia with infants showing an apparent lack of awareness of their surroundings. Common features are intrauterine and postnatal growth delay, an emaciated appearance with hypotrophy, microcephaly with a narrow skull and dolichocephaly, microretrognathia, hypertelorism, and poorly modeled and angular ears. Foot anomalies include pes equinovarus and/or rocker-bottom feet and the fingers overlap (the fifth and second fingers with the fourth and third). Malformations are common with involvement of the eyes (microphthalmia, coloboma), heart (over 90% of cases) digestive tract (esophageal atresia, anorectal malformations), kidneys and urinary tract (hydronephrosis, uni- or bilateral agenesis). Less frequently, cleft/lip palate, arthrogryposis, radial aplasia, spina bifida and anencephaly, holoprosencephaly and omphalocele are observed. The majority of cases are associated with free trisomy 18. Mosaic trisomy 18 has been detected in a few patients presenting with a clinical picture that varies from classical trisomy 18 to a normal phenotype depending on the number of trisomic cells present in the tissues. The trisomy 18 phenotype appears to be associated with the presence of three copies of the 18q11-q12 interval. The risk of recurrence of trisomy (21, 13 or 18) in families of an index case with trisomy 18 is around 1%. However, in families in which trisomy 18 is caused by translocation, the recurrence risk is higher if one of the parents is a carrier of a balanced translocation. Trisomy 18 may be suspected during pregnancy from ultrasound findings (growth retardation, malformations, multiple choroid plexus cysts) and can be confirmed by karyotype analysis of the fetus. Serum markers (used for the diagnosis of trisomy 21) may also be abnormal. Management is supportive only. Surgical treatment of the malformations does little to improve the poor prognosis associated with this syndrome: 90% of infants die within the first year of life from cardiac, renal or neurological complications, or from repeated infections. Prolonged survival (in some cases into adulthood) has been reported, mainly in cases involving mosaic or partial trisomy (resulting from translocation). The majority of non-mosaic patients develop only limited autonomy (absence of speech and ambulation). The growth retardation is significant. (Source: Orphanet)
Link: trisomy 18 syndrome
(Renal dysplasia - mesomelia - radiohumeral fusion)
Ulbright-Hodes syndrome is characterised by renal dysplasia; growth retardation; phocomelia or mesomelia; radiohumeral fusion; rib abnormalities; anomalies of the external genitalia and a potter-like facies. The syndrome has been described in three infants (one pair of sibs and an unrelated case); all of whom died shortly after birth from respiratory distress resulting from pulmonary hypoplasia and oligohydramnios caused by renal dysplasia. The mode of transmission appears to be autosomal recessive. (Source: Orphanet)
Link: Ulbright-Hodes syndrome
Ulnar hemimelia is a congenital ulnar deficiency of the forearm characterized by complete or partial absence of the ulna bone. Incidence is estimated at 1/100,000-150,000 live births, with a male to female ratio of 3:2. Ulnar hemimelia is unilateral in approximately 70% of cases, tends to be right-sided, and is usually incomplete and nonsyndromic. Most patients have some shortening of the forearm. The position of the hand tends to drift to the ulnar-side of the wrist. The extension of the elbow is generally limited to about 90 degrees. In severe cases, the elbow is held at about 160 degrees of flexion. Ulnar hemimelia may present with other skeletal anomalies (absence or hyperplasia of the radial digits, thumb duplication, or syndactyly) or as part of a syndrome (Poland anomaly, Goltz-Gorlin syndrome, Schinzel syndrome, Klippel-Feil syndrome or Cornelia de Lange syndrome; see these terms). Ulnar deficiency is also one of the manifestations of the femur-fibula-ulna syndrome (see this term). The etiology of ulnar hemimelia remains unknown. The deformity is believed to develop between the 4th and 7th week of gestation. Most of the reported cases are sporadic but a few familial cases have been described. Diagnosis is based on clinical examination and X-rays. Further tests may be required in case of additional anomalies. The differential diagnosis should include a short ulna, dyschondrogenesis, Madelung deformity, Nievergelt syndrome and embryofetopathy due to maternal diabetes mellitus (see these terms). Treatment depends on the severity of the condition and the associated skeletal anomalies or syndromes. Passive stretching exercises may allow extension of the wrist and elbow to a normal position. Corrective casting and splinting may also be used. In severe cases, surgical therapy aimed at ulnar lengthening (surgical excision, osteotomy, or plastic surgery) is necessary. Occupational and physical therapy is mandatory. Patients with ulnar hemimelia may have limited motion, function and strength, but in general, the limb and hand are functional. In case of syndromic presentation, prognosis depends on the nature of the associated anomalies. (Source: Orphanet)
Link: Ulnar hemimelia
Thrombocytopenia-absent radius syndrome
Thrombocytopenia-absent radius (TAR) syndrome is a very rare congenital malformation syndrome characterized by bilateral radial aplasia and thrombocytopenia. It occurs in less than 1 per 100,000 live births, equally affecting both sexes. TAR syndrome presents with bilateral absence of the radius with present thumbs (that is the major distinguishing feature making TAR syndrome different from other disorders featuring radial aplasia), thrombocytopenia, and a number of additional features including skeletal and cardiac anomalies. Ulnar or humeral anomalies, and phocomelia in the most severe cases, may be present. Lower limbs may also be involved (dislocation of the patella and/or of the hips, absent tibiofibular joint, and lower limb phocomelia). Hypomegakaryocytic thrombocytopenia is present in all cases. Most affected individuals have bruising at birth, and typically present with petechiae and severe bleeding (gastrointestinal and, rarely, intracerebral) during the first years of life. Gradually over childhood the number of platelets increases and by adulthood the blood platelet count may be nearly normal or completely normal. Cow's milk intolerance (manifesting by persistent diarrhea and failure to thrive) is frequent. Congenital heart defects (atrial and/or ventricular septal defect, patent arterial duct, tetralogy of Fallot) occur in 15-30% of patients. Dysmorphic features (micrognathia, tall and broad forehead, low and posteriorly rotated ears) and renal malformations have been observed. Intellectual deficit is reported in less than 10% of patients (usually due to intracranial hemorrhage). The etiology and inheritance pattern remain unclear. Autosomal recessive and autosomal dominant inheritance with variable penetrance have been suggested. In all patients, a deletion on chromosome 1q21.1 has been found. However, at present, it is still unclear how this relates to the cause in TAR syndrome. Diagnosis is made on the basis of the pattern of limb abnormality and associated features. Skeletal X-ray and examination of blood and bone marrow confirm the diagnosis. Prenatal diagnosis may be carried out using ultrasonography. The main differential diagnoses include Holt-Oram syndrome, Roberts syndrome, Fanconi anemia, thalidomide embryopathy and RAPADILINO syndrome (see these terms). There is no specific treatment for TAR syndrome. Prevention of bleeding and hemorrhage in the first years of life is essential to reduce the clinically significant morbidity. Severe thrombocytopenia may require platelet transfusions. Surgical interventions may be required to treat cardiac, urinary or skeletal malformations. Plastic surgery, occupational therapy and physiotherapy should be offered. (Source: Orphanet)
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